Influenza is an acute respiratory infectious disease that is caused by influenza virus and could seriously harm the health of human beings. Influenza viruses include three types of (A), (B) and (C), wherein the antigenicity of influenza A virus varies a lot, and has multiple times caused global pandemic in history. Influenza virus A also spreads among pigs and birds, and causes influenza pandemic and the death of numerous animals, while human influenza virus B and human influenza virus C only spread among human beings. Influenza virus B is of low pathogenicity against human beings, and Influenza virus C mainly attacks infants and children, and usually cannot cause influenza epidemic. According to the estimation of WHO, during the explosive epidemic of influenza, the influenza viruses could rapidly spread over the whole world, and affect 10%-20% of the whole population. Even in the years of non-explosive influenza epidemic, they would bring about 3 to 5 million serious cases and 250 to 500 thousand deaths each year.
So far, influenza vaccination is the most effective means for controlling influenza. The vaccination against influenza could not only reduce the incidence and death rate of high-risk population, but also could alleviate symptoms and reduce the occurrence rate of complications and the possibility of transmission.
Live attenuated influenza vaccines are immunized via the route of nasal mucosa, and has the advantage of mimicking natural infection. As compared with inactivated vaccines, live attenuated influenza vaccines, in addition to inducing humoral immunity, could also induce local neutralizing antibody and cellular immune response, which lasts for a long time. In addition, live attenuated influenza vaccines are easy to use, and are easily to be immunized in large scale.
Live attenuated influenza vaccines are usually formulated into freeze-dried powder injection. Although free-drying technique is mature, it still has the following defects: first, free-dried powder injection needs to be reconstituted before use, which is not easy to use and increases the possibility of being polluted; second, the freeze-drying process of biological products is complicated and time-consuming, and causes big loss of influenza virus titer; and third, vacuum freeze-drying equipment requires large investment, high energy consumption and high costs, but has limited vaccine production capacity, and especially in the outbreak of influenza, it is difficult for the vaccine manufacturers to produce sufficient doses of vaccine in a short time.
In 2003, MedImmune Company's attenuated influenza vaccine, FluMist, was approved by FDA. The product is a cold-adapted trivalent viral vaccine, and is an aqueous solution for injection. The product needs to be stored and transported at a temperature of about 15° C. and below, which limits the large-scale application of FluMist because pharmacies or schools usually do not have the equipment for handling frozen products.
In 2005, MedImmune Vaccines Inc. filed a patent application entitled “Refrigerator-Temperature Stable Influenza Vaccine Compositions” (Patent Application No. PCT/US2005/035614), providing liquid formulations comprising a hydrolyzed gelatin component that can stabilize the influenza vaccine at temperatures ranging from 4° C. to 8° C. Nevertheless, the gelatin or gelatin derivatives in the formulations can directly cause allergy and non-cellular mediated immune responses in vaccines.
Therefore, in order to overcome the defects of the high cost in freeze-drying technology and the allergic reaction and immune response that are easily caused by hydrolyzed gelatin component, there is need to develop a gelatin-free protectant for a liquid vaccine formulation and a live attenuated influenza vaccine containing the same.